HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 22, 21183-21193, June 3, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/22/21183    most recent M501087200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Huang, S. Articles by Hansen, T. H. Search for Related Content PubMed PubMed Citation Articles by Huang, S. Articles by Hansen, T. H. Social Bookmarking                      What's this?

Evidence for MR1 Antigen Presentation to Mucosal-associated Invariant T Cells^*

Shouxiong Huang, Susan Gilfillan, Marina Cella, Michael J. Miley, Olivier Lantz, Lonnie Lybarger¶, Daved H. Fremont, and Ted H. Hansen||

From the Department of Pathology and Immunology, Washington University, St. Louis, Missouri 63110, Laboratoire d'Immunologie and INSERM U520, XCInstitut Curie, 26 rue d'Ulm, Paris, France, and ^¶Department of Cell Biology and Anatomy, University of Arizona Health Sciences Center, Tucson, Arizona 85724-5044

The novel class Ib molecule MR1 is highly conserved in mammals, particularly in its 1/2 domains. Recent studies demonstrated that MR1 expression is required for development and expansion of a small population of T cells expressing an invariant T cell receptor (TCR) chain called mucosal-associated invariant T (MAIT) cells. Despite these intriguing properties it has been difficult to determine whether MR1 expression and MAIT cell recognition is ligand-dependent. To address these outstanding questions, monoclonal antibodies were produced in MR1 knock-out mice immunized with recombinant MR1 protein, and a series of MR1 mutations were generated at sites previously shown to disrupt the ability of class Ia molecules to bind peptide or TCR. Here we show that 1) MR1 molecules are detected by monoclonal antibodies in either an open or folded conformation that correlates precisely with peptide-induced conformational changes in class Ia molecules, 2) only the folded MR1 conformer activated 2/2 MAIT hybridoma cells tested, 3) the pattern of MAIT cell activation by the MR1 mutants implies the MR1/TCR orientation is strikingly similar to published major histocompatibility complex/TCR engagements, 4) all the MR1 mutations tested and found to severely reduce surface expression of folded molecules were located in the putative ligand binding groove, and 5) certain groove mutants of MR1 that are highly expressed on the cell surface disrupt MAIT cell activation. These combined data strongly support the conclusion that MR1 has an antigen presentation function.

Received for publication, January 31, 2005 , and in revised form, March 9, 2005.

^* This work was supported by National Institutes of Health Grants AI46553 and AI19687. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^|| To whom correspondence should be addressed: Dept. of Pathology and Immunology, WA University School of Medicine, 4566 Scott Ave., St. Louis, MO 63110. Tel.: 314-362-2716; Fax: 314-362-4137; E-mail: hansen{at}pathology.wustl.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. Huang, E. Martin, S. Kim, L. Yu, C. Soudais, D. H. Fremont, O. Lantz, and T. H. Hansen MR1 antigen presentation to mucosal-associated invariant T cells was highly conserved in evolution PNAS, May 19, 2009; 106(20): 8290 - 8295. [Abstract] [Full Text] [PDF]

				S. Huang, S. Gilfillan, S. Kim, B. Thompson, X. Wang, A. J. Sant, D. H. Fremont, O. Lantz, and T. H. Hansen MR1 uses an endocytic pathway to activate mucosal-associated invariant T cells J. Exp. Med., May 12, 2008; 205(5): 1201 - 1211. [Abstract] [Full Text] [PDF]

				G. Wingender and M. Kronenberg Role of NKT cells in the digestive system. IV. The role of canonical natural killer T cells in mucosal immunity and inflammation Am J Physiol Gastrointest Liver Physiol, January 1, 2008; 294(1): G1 - G8. [Abstract] [Full Text] [PDF]

				I. Kawachi, J. Maldonado, C. Strader, and S. Gilfillan MR1-Restricted V{alpha}19i Mucosal-Associated Invariant T Cells Are Innate T Cells in the Gut Lamina Propria That Provide a Rapid and Diverse Cytokine Response J. Immunol., February 1, 2006; 176(3): 1618 - 1627. [Abstract] [Full Text] [PDF]